Seaton M J, Plopper C G, Bond J A
Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709, USA.
Toxicology. 1996 Oct 28;113(1-3):314-7. doi: 10.1016/0300-483x(96)03464-6.
1,3-Butadiene (BD) is oxidized by cytochrome P450 to reactive metabolites, including 1,2-epoxy-3-butene (BMO) and 1,2:3,4-diepoxybutane (BDE), which are thought to be responsible for BD genotoxicity and carcinogenicity. Alveolar-bronchiolar neoplasms were observed in mice but not rats following chronic exposure to BD. The site-specific carcinogenicity of BD in mice may result from metabolic activation in pulmonary tissue. We have incubated bronchioles isolated from both male B6C3F1 mice and male Sprague-Dawley rats with 34 microM BD (final concentration in the aqueous reaction medium) to assess species differences in pulmonary metabolism of BD and to enhance our understanding of species- and site-dependent BD carcinogenicity. Bronchioles from both mice and rats formed BMO, although mouse tissue produced 2-fold more than rat tissue. These preliminary results suggest that pulmonary activation of BD may play a role in the carcinogenicity of BD following inhalation exposure; however, other factors in addition to metabolic differences, probably contribute to the observed differences in susceptibility to BD toxicity.
1,3 - 丁二烯（BD）被细胞色素P450氧化生成反应性代谢产物，包括1,2 - 环氧 - 3 - 丁烯（BMO）和1,2:3,4 - 二环氧丁烷（BDE），这些代谢产物被认为是BD具有遗传毒性和致癌性的原因。在慢性暴露于BD后，在小鼠而非大鼠中观察到肺泡 - 细支气管肿瘤。BD在小鼠中的位点特异性致癌性可能源于肺组织中的代谢活化。我们用34微摩尔BD（水反应介质中的终浓度）孵育从雄性B6C3F1小鼠和雄性斯普拉 - 道利大鼠分离的细支气管，以评估BD肺代谢中的种属差异，并加深我们对种属和位点依赖性BD致癌性的理解。小鼠和大鼠的细支气管都形成了BMO，尽管小鼠组织产生的量是大鼠组织的2倍。这些初步结果表明，BD的肺激活可能在吸入暴露后BD的致癌性中起作用；然而，除了代谢差异之外的其他因素可能导致观察到的对BD毒性易感性的差异。
